Characterization of a clinical cohort of patients with Primary Progressive Aphasia: the role of Screening for Aphasia in NeuroDegeneration in clinical assessment

Primary Progressive Aphasia (PPA) is a neurodegenerative syndrome characterized by an insidious and progressive impairment of language, while other cognitive domains are initially preserved. The classification of PPA into its three main variants - semantic (svPPA), nonfluent/agrammatic (nfvPPA), and logopenic (lvPPA) - is based on distinct language profiles and corresponding neuroanatomical patterns. In recent years, the Screening for Aphasia in NeuroDegeneration (SAND) has emerged as a useful tool for detecting and quantifying language deficits associated with neurodegenerative conditions in Italian-speaking patients. This study aims to characterize the language profiles of PPA by analyzing SAND performance both across and within the three clinical variants, in order to capture intra- and inter-group patterns of language impairment. In parallel, it examines the neuroanatomical correlates of the tasks, to test the hypothesis that specific language deficits, detected by this tool, map onto distinct patterns of brain atrophy. By integrating behavioral and neuroimaging data, this approach seeks to explore the relationship between language dysfunction and structural brain changes in PPA, with the goal of contributing to a better understanding of the disorder’s clinical and anatomical variability. Forty-nine consecutive patients with a clinical diagnosis of PPA were recruited and classified into one of the three variants based on current diagnostic criteria. All patients underwent a comprehensive SAND assessment and a subgroup of patients also underwent the MRI scan. SvPPA patients showed deficits in picture naming and single-word comprehension, in line with the known degradation of semantic memory. NfvPPA and lvPPA patients exhibited prominent impairments in sentence repetition, reflecting deficits in motor speech planning and phonological loop integrity, respectively. Neuroanatomical findings revealed a correlation between naming performance and atrophy in the anterior temporal lobe, consistently aligning with its well-established involvement in semantic memory. Notably, we observed a significant correlation between single-word comprehension deficits and left cerebellar (crus I and II) atrophy, as well as between writing impairments and cerebellar (left crus I) volume loss across all three PPA variants; these findings are only partially described in existing literature, and may point to a broader role of the cerebellum in language processing. In conclusion, our findings confirm the expected patterns of language impairment and neurodegeneration. The involvement of the left cerebellum in language tasks, such as word comprehension and writing, supports the new questions recently emerged on the cerebellar contribution to higher-order cognitive functions and may warrant further investigation.